Protocol for measuring myocardial blood flow by PET/CT in cats

Purpose: The aim of this study was to establish a protocol for measuring myocardial blood flow (MBF) by PET/CT in healthy cats. The rationale was its future use in Maine Coon cats with hypertrophic cardiomyopathy (HCM) as a model for human HCM. Methods: MBF was measured in nine anaesthetized healthy cats using a PET/CT scanner and 13NH3 at rest and during adenosine infusion. Each cat was randomly assigned to receive vasodilator stress with two or three adenosine infusions at the following rates (μg/kg per minute): 140 (Ado1, standard rate for humans), 280 (Ado2, twice the human standard rate), 560 (Ado4), 840 (Ado6) and 1,120 (Ado8). Results: The median MBF at rest was 1.26ml/min per g (n = 9; range 0.88-1.72ml/min per g). There was no significant difference at Ado1 (n = 3; median 1.35, range 0.93-1.55ml/min per g; ns) but MBF was significantly greater at Ado2 (n = 6; 2.16, range 1.35-2.68ml/min per g; p < 0.05) and Ado4 (n = 6; 2.11, 1.92-2.45ml/min per g; p < 0.05). Large ranges of MBF values at Ado6 (n = 4; 2.53, 2.32-5.63ml/min per g; ns) and Ado8 (n = 3; 2.21, 1.92-5.70ml/min per g; ns) were noted. Observed adverse effects, including hypotension, AV-block and ventricular premature contractions, were all mild, of short duration and immediately reversed after cessation of the adenosine infusion. Conclusion: MBF can be safely measured in cats using PET. An intravenous adenosine infusion at a rate of 280μg/kg per minute seems most appropriate to induce maximal hyperaemic MBF response in healthy cats. Higher adenosine rates appear less suitable as they are associated with a large heterogeneity in flow increase and rate pressure product, most probably due to the large variability in haemodynamic and heart rate respons

Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia

Purpose: Tetrahydrobiopterin (BH4) is an essential co-factor for the synthesis of nitric oxide (NO), and BH4 deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH4 deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia. Methods: Myocardial blood flow (MBF; mlmin−1g−1) was measured at rest, during adenosine-induced (140μgkg−1min−1 over 7min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using 15O-labelled water and positron emission tomography. Measurements were repeated 60min later, after intravenous infusion of BH4 (10mgkg−1 body weight over 30min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress. Results: BH4 increased exercise-induced hyperaemia in controls (2.96±0.58vs 3.41±0.73mlmin−1g−1, p<0.05) and hypercholesterolaemic subjects (2.47±0.78vs 2.70±0.72mlmin−1g−1, p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52±1.10vs 4.85±0.45mlmin−1g−1, p=NS) or hypercholesterolaemic subjects (4.86±1.18vs 4.53±0.93mlmin−1g−1, p=NS). Flow reserve utilisation remained unchanged in controls (70±17% vs 71±19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53±15% vs 66±14%, p<0.05). Conclusion: BH4 restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH4 deficiency may contribute to coronary microcirculatory dysfunction in hypercholesterolaemi

Assessment of myocardial perfusion by dynamic O-15-labeled water PET imaging: Validation of a new fast factor analysis

Background: Factor analysis (FA) is an established method for separating myocardium from blood pool by use of oxygen 15-labeled water and positron emission tomography for analyzing myocardial blood flow (MBF). Conventional FA methods generating images from sinograms (sinoFA) are time-consuming, whereas FA can be performed on the reconstructed images (reconFA) in a fraction of time. We validated the MBF values obtained by reconFA versus sinoFA. Methods and Results: In 23 volunteers (mean age, 26.6±3.4 years) MBF was calculated from sinoFA and reconFA and blindly reanalyzed 1 month later by the same observer. Intraobserver agreement and reconFA-versus-sinoFA agreement were assessed according to Bland and Altman (BA). Reproducibility proved excellent for global sinoFA (r=0.968; P<.001; BA limits, −0.617 to 0.676 mL·min−1·g−1) and slightly superior for reconFA (r=0.979; P<.001; BA limits, −0.538 to 0.558 mL·min−1·g−1), with wider limits of agreement for segmental MBF from sinoFA (r=0.777; P<.001; BA limits, −1.676 to 1.656 mL·min−1·g−1) and reconFA (r=0.844; P<.001; BA limits, −1.999 to 1.992 mL·min−1·g−1). In addition, sinoFA and reconFA showed excellent correlation (r=0.975, P<.001) and agreement (BA limits, −0.528 to 0.648 mL·min−1·g−1) for global and segmental values (r=0.955; P<.001; BA limits, −1.371 to 1.491 mL·min−1·g−1). Conclusions: Use of reconFA allows rapid and reliable quantitative MBF assessment with O-15-labeled wate

Mini volume collapse as evidence for a three-body magnetic polaron in S m1-x e ux S

Samarium sulfide (SmS) is a nonmagnetic narrow-gap (0.06 eV) semiconductor that undergoes a transition to a metallic intermediate valence state at 6.5 kbar. Europium sulfide (EuS) is a ferromagnetic semiconductor with a Curie temperature of 16 K and a gap of 1.6 eV. Here we present a study of the lattice constant, magnetic susceptibility, and resistivity of the substitution series Sm1-xEuxS for 0 \u3c x \u3c 1. We observe a smooth interpolation of magnetic and transport behavior across the series, consistent with a virtual crystal scenario and Vegard\u27s law. Surprisingly, however, the lattice constant deviates below Vegard\u27s law in a manner that suggests parametric control of the Sm-Sm distance by the Eu moment in the manner of a magnetic polaron

13N-ammonia myocardial perfusion imaging with a PET/CT scanner: impact on clinical decision making and cost-effectiveness

Purpose: The purpose of the study is to determine the impact of 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) on clinical decision making and its cost-effectiveness. Materials and methods: One hundred consecutive patients (28 women, 72 men; mean age 60.9 ± 12.0years; range 24-85years) underwent 13N-ammonia PET scanning (and computed tomography, used only for attenuation correction) to assess myocardial perfusion in patients with known (n = 79) or suspected (n = 8) coronary artery disease (CAD), or for suspected small-vessel disease (SVD; n = 13). Before PET, the referring physician was asked to determine patient treatment if PET would not be available. Four weeks later, PET patient management was reassessed for each patient individually. Results: Before PET management strategies would have been: diagnostic angiography (62 of 100 patients), diagnostic angiography and percutaneous coronary intervention (PCI; 6 of 100), coronary artery bypass grafting (CABG; 3 of 100), transplantation (1 of 100), or conservative medical treatment (28 of 100). After PET scanning, treatment strategies were altered in 78 patients leading to: diagnostic angiography (0 of 100), PCI (20 of 100), CABG (3 of 100), transplantation (1 of 100), or conservative medical treatment (76 of 100). Patient management followed the recommendations of PET findings in 97% of the cases. Cost-effectiveness analysis revealed lower costs of €206/patient as a result of PET scanning. Conclusion: In a population with a high prevalence of known CAD, PET is cost-effective and has an important impact on patient managemen

Diagnostic accuracy of myocardial perfusion imaging with single photon emission computed tomography and positron emission tomography: a comparison with coronary angiography

Objective The aim of this study was to compare the diagnostic accuracy of myocardial perfusion imaging (MPI) by positron emission tomography (PET) with the diagnostic accuracy of MPI by single photon emission computed tomography (SPECT) in two comparable patient cohorts, using coronary angiography (CA) as the standard of reference. Methods A "SPECT-group” of 80 patients (15 female, 65 male; mean age 60±9years) and a "PET-group” of 70 patients (14 female, 56 male; mean age 57±10years) underwent a one day stress/rest examination either with attenuation-corrected 13N-ammonia PET or attenuation-corrected 201TlCl SPECT or 99mTc-hexakis-methoxy-isobutyl-isonitril (MIBI) SPECT. PET and SPECT results were semiquantitatively graded using a 6-segment heart model. All patients underwent CA, and stenoses were graded as a diameter reduction ≥50%. Results Coronary findings between both groups did not significantly differ at CA. For the SPECT-group overall sensitivity and specificity for localisation of stenoses was 77% and 84%. Respective values for the PET-group were 97% and 84%. The specificity of MPI by SPECT in the detection of ischemia was 74% and 91% for MPI by PET. The diagnostic accuracy of MPI improves when the individual coronary dominance and previous coronary revascularisations are taken into account. Conclusion MPI by 13N-ammonia PET is more sensitive in the detection and localisation of coronary stenoses, and more specific in the detection of ischemia than MPI by 201TlCl/99mMIBI SPEC

Effects of AV delay programming on ventricular resynchronisation: role of radionuclide ventriculography

Purpose: Optimal atrioventricular delay (AVD) setting for cardiac resynchronisation therapy, i.e. biventricular pacing in patients with heart failure, remains a formidable challenge. Thus, the purpose of this study was to evaluate the effects of different AVD on inter- and intra-ventricular resynchronisation using phase histograms of radionuclide ventriculography (RNV). Methods: In 17 consecutive patients (mean age 64 ± 6years), RNV was performed 236 ± 350days after pacemaker implantation for cardiac resynchronisation therapy. Images were acquired during atrial pacing at 80bpm and during biventricular pacing with AVD ranging from 80 to 160ms. Inter-ventricular dyssynchrony was measured by the delay between the mean phase angles of the left and right ventricles. Intra-ventricular dyssynchrony was measured by the standard deviation (SD) of left ventricular phase histograms. Results: Left ventricular (LV) ejection fraction (EF) was inversely correlated to LV dyssynchrony (SD of LV phase histogram, R = −0.82, p < 0.0001). However, the increase in LVEF by biventricular pacing (mean +4.4 ± 4%) showed only modest correlation to the resulting resynchronisation effect (characterised by a −13 ± 8° decrease in LV phase histogram SD, R = −0.38, p < 0.0001). Conclusion: RNV is helpful in optimising pacing parameters for resynchronisation therapy. Varying AVD did not have a major impact on intra- or inter-ventricular resynchronisation. Thus, the benefit of AVD-based LVEF optimisation seems to result from atrioventricular resynchronisatio